Ara h 2-specific IgE epitope-like peptides inhibit the binding of IgE to Ara h 2 and suppress lgE-dependent effector cell activation

Korošec, Peter (avtor), Koren, Ana (avtor), Debeljak, Jerneja (avtor), Zahirović, Abida (avtor), Skerbinjek-Kavalar, Maja (avtor), Berce, Vojko (avtor), Dejanović, Luka (avtor), Luzar, Jernej (avtor), Štrukelj, Borut (avtor), Lunder, Mojca (avtor)

Background: Clinical and experimental analyses indicate a pathognomonic role for allergen IgE crosslinking through epitope–paratope interactions as a major initial step in the cascade leading to effector cell activation and clinical manifestations of lgE-mediated food allergies. We aimed to undertake the initial development and assessment of Ara h 2-specific IgE epitope-like peptides that can bind to allergenspecific IgE paratopes and suppress effector cell activation. Methods: We performed biopanning, screening, IgE binding, selection and mapping of peptides. We generated synthetic peptides for use in all functional experiments. ImmunoCAP inhibition, basophil and mast cell activation tests, with LAD2 cells, a human mast cell line were performed. Twenty-six children or young adults who had peanut allergy were studied. Results: We identified and selected three linear peptides (DHPRFNRDNDVA, DHPRYGP and DHPRFST), and immunoblot analyses revealed binding to lgE from peanut-allergic individuals. The peptide sequences were aligned to the disordered region corresponding to the loop between helices 2 and 3 of Ara h 2, and conformational mapping showed that the peptides match the surface of Ara h 2 and h 6 but not other peanut allergens. In ImmunoCAP inhibition experiments, the peptides significantly inhibit the binding of IgE to Ara h 2 (p < .001). In basophil and mast cell activation tests, the peptides significantly suppressed Ara h 2-induced effector cell activation (p < .05) and increased the half-maximal Ara h 2 effective concentration (p < .05). Binding of the peptides to specific IgEs did not induce activation of basophils or mast cells. Conclusions: These studies show that the indicated peptides reduce the allergenic activity of Ara h 2 and suppress lgE-dependent basophil and mast cell activation. These observations may suggest a novel therapeutic strategy for food allergy based on epitope–paratop blocking.

• Jezik: Angleški jezik
• Ključne besede: Ara h 2, ImmunoCAP inhibition, basophil activation test, epitopes, mast cell activation test, paratopes, peanut allergy, peptides, specific IgE
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: Str. 636-647
• Številčenje: Vol. 53, iss. 6
• PID: 20.500.12556/RUL-147382
• UDK: 616-056.43
• ISSN pri članku: 1365-2222
• DOI: 10.1111/cea.14314
• COBISS.SI-ID: 151992835
• Datum objave v RUL: 03.07.2023

Gradivo je del revije

• Naslov: Clinical & experimental allergy
• Skrajšan naslov: Clin. exp. allergy
• Založnik: Wiley
• ISSN: 1365-2222
• COBISS.SI-ID: 515014681

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: alergeni, Ara h 2, test aktivacije bazofilcev, epitopi, inhibicija ImmunoCAP, test aktivacije mastocitov, paratopi, alergija na arašide, peptidi, specifični IgE

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P3-0360
• Naslov: Celostna obravnava alergijskih bolezni in astme v Sloveniji: od epidemiologije do genetike

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P4-0127
• Naslov: Farmacevtska biotehnologija: znanost za zdravje